fisiologi penuaan dr dian
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Physiology of AgingPhysiology of Aging
Laboratorium Fisiologi
FK UNEJ
http://www.anti-aging.org/blog/aging_3.jpg
ObjectivesObjectives
Discuss the Characteristics of AgingDiscuss the Characteristics of Aging
Review the various Theories of AgingReview the various Theories of Aging
Explore the effects of Aging on the different Explore the effects of Aging on the different
organ systemsorgan systems
PenuaanPenuaan
Definisi Menua => Definisi Menua => Suatu proses menghilangnya secara perlahan Suatu proses menghilangnya secara perlahan
perlahan kemampuan jaringan untuk perlahan kemampuan jaringan untuk memperbaiki diri/mengganti diri dan memperbaiki diri/mengganti diri dan mempertahankan struktur dan fungsi mempertahankan struktur dan fungsi normalnya sehingga tidak dapat bertahan normalnya sehingga tidak dapat bertahan terhadap jejas dan memperbaiki kerusakan terhadap jejas dan memperbaiki kerusakan yang diderita (constantinedes,1994)yang diderita (constantinedes,1994)
CHARACTERISTICS OF AGINGCHARACTERISTICS OF AGING
Mortality increases exponentiallyMortality increases exponentially Biochemical composition of tissue changesBiochemical composition of tissue changes Physiologic capacity decreasesPhysiologic capacity decreases Ability to maintain homeostasis diminishesAbility to maintain homeostasis diminishes Susceptibility and vulnerability to disease Susceptibility and vulnerability to disease
increasesincreases
Environmental and Genetic factorsEnvironmental and Genetic factorsinfluence the rate of aginginfluence the rate of aging
THEORIES OF AGING: THEORIES OF AGING: OXIDATIVE STRESSOXIDATIVE STRESS
Synopsis:Synopsis: Oxygen converted during metabolism Oxygen converted during metabolism causes protein, lipid, and DNA damage over timecauses protein, lipid, and DNA damage over time
In support:In support: Mutations in oxidative stress pathway can extend life Mutations in oxidative stress pathway can extend life
spanspan Mutations in other pathways that increase longevity Mutations in other pathways that increase longevity
resist oxidative damageresist oxidative damage
In opposition:In opposition: Antioxidants do not delay human Antioxidants do not delay human senescence or diseasesenescence or disease
THEORIES OF AGING: THEORIES OF AGING: IMMUNOLOGICIMMUNOLOGIC
Synopsis:Synopsis: Time-acquired deficits, primarily in T-Time-acquired deficits, primarily in T-cell function, increase susceptibility to infections cell function, increase susceptibility to infections and cancerand cancer
In support:In support: Some diseases are associated with Some diseases are associated with agingaging
In opposition:In opposition: Immunologic function is apparently Immunologic function is apparently not directly related to healthy agingnot directly related to healthy aging
THEORIES OF AGING: THEORIES OF AGING: GENETICGENETIC
Synopsis:Synopsis: Senescence results from activation or suppression Senescence results from activation or suppression of specific of specific ““agingaging”” genes genes
In support:In support: Longevity appears to be hereditableLongevity appears to be hereditableSome genetic disorders lead to accelerated agingSome genetic disorders lead to accelerated aging
In opposition: In opposition: Evolutionary pressures appear to select for reproductive Evolutionary pressures appear to select for reproductive
fitness rather than senescencefitness rather than senescenceLittle direct evidence of Little direct evidence of ““genetic programminggenetic programming”” of of
senescence in humanssenescence in humans
Aging effects on organ Aging effects on organ systemssystems
CardiovascularCardiovascular
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Cardiovascular: StructureCardiovascular: Structure
Age-associated changeAge-associated change Possible disease Possible disease outcomesoutcomes
↑ ↑ vascular intimal thickeningvascular intimal thickening Early stages of atherosclerosisEarly stages of atherosclerosis
↑ ↑ vascular stiffnessvascular stiffness Systolic HTNSystolic HTN
StrokeStroke
AtherosclerosisAtherosclerosis
↑ ↑ LV wall thicknessLV wall thickness ↓↓ early diastolic cardiac fillingearly diastolic cardiac filling
↑ ↑ cardiac filling pressurecardiac filling pressure
Lower threshold for dyspneaLower threshold for dyspnea
↑ ↑ Left Atrial sizeLeft Atrial size Lone Atrial FibrillationLone Atrial Fibrillation
Cardiovascular: FunctionCardiovascular: Function
Age-associated changeAge-associated change Possible disease outcomesPossible disease outcomes
Altered regulation of vascular Altered regulation of vascular tonetone
Vascular stiffeningVascular stiffening
HypertensionHypertension
Decreased cardiovascular Decreased cardiovascular reservereserve
Lower threshold for and Lower threshold for and increased severity of heart increased severity of heart failurefailure
PulmonaryPulmonary
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Pulmonary - StructurePulmonary - Structure
↓ ↓ Alveoli and lung capillariesAlveoli and lung capillaries ↓ ↓ Number and elasticity of parenchymal elastic fibers Number and elasticity of parenchymal elastic fibers
→ Gradual loss of elastic recoil of the lungs→ Gradual loss of elastic recoil of the lungs Airway size ↓Airway size ↓ Ciliary action less effectiveCiliary action less effective Chest wall stiffensChest wall stiffens Respiratory muscles weakenRespiratory muscles weaken ↓ ↓ lung masslung mass Diaphragm weakens by 25%Diaphragm weakens by 25%
Pulmonary - FunctionPulmonary - Function
Pulmonary – FunctionPulmonary – Function
↓ ↓ FEVFEV11 and FVC and FVC ↑ ↑ Residual volumeResidual volume Ventilation-Perfusion mismatching causes ↓ Ventilation-Perfusion mismatching causes ↓
PaOPaO2 2 [100 – (0.32 * age)][100 – (0.32 * age)]
Maximum inspiratory and expiratory Maximum inspiratory and expiratory pressures ↓pressures ↓
Diffusion of CO decreasedDiffusion of CO decreased Decreased ventilatory response to hypercapniaDecreased ventilatory response to hypercapnia
RenalRenal
Renal - StructureRenal - Structure
↓ ↓ Renovascular bed → ↓ Renal Blood flowRenovascular bed → ↓ Renal Blood flow
Selective loss of cortical vasculatureSelective loss of cortical vasculature
Renal mass ↓ 25% - mainly corticalRenal mass ↓ 25% - mainly cortical
Renal weight ↓Renal weight ↓
Renal - FunctionRenal - Function
↓ ↓ Cr clearance & GFR (10mL/decade) → ↓ Cr clearance & GFR (10mL/decade) → ↓ excretion of drugs, toxinsexcretion of drugs, toxins
↓ ↓ concentrating and diluting capacityconcentrating and diluting capacity ↓ ↓ serum renin and aldosterone (30-50%) serum renin and aldosterone (30-50%)
→ → fluid and electrolyte abnormalities - ↑ volume fluid and electrolyte abnormalities - ↑ volume depletion and dehydrationdepletion and dehydration
→ ↑ → ↑ risk of hyerkalemiarisk of hyerkalemia
→ ↓ → ↓ Na & K excretion and conservationNa & K excretion and conservation ↓ ↓ vitamin D activationvitamin D activation
GIGI
GI - StructureGI - StructureAge-associated changeAge-associated change Possible disease Possible disease
outcomesoutcomes↓ ↓ liver size and blood flowliver size and blood flow Impaired clearance of drugs Impaired clearance of drugs
requiring phase I metabolismrequiring phase I metabolism
Impaired response to gastric Impaired response to gastric mucosal injurymucosal injury
Increased risk of gastric & Increased risk of gastric & duodenal ulcersduodenal ulcers
↓↓ pancreatic mass and enzyme pancreatic mass and enzyme reservesreserves
Increased insulin resistanceIncreased insulin resistance
↓↓ in effective colonic contractionsin effective colonic contractions ConstipationConstipation
↓↓ in gut-associated lymphoid tissuein gut-associated lymphoid tissue Increased risk of gastric & Increased risk of gastric & duodenal ulcersduodenal ulcers
GI - FunctionGI - FunctionAge-associated changeAge-associated change Possible disease Possible disease
outcomesoutcomes↓↓ stomach acid productionstomach acid production Atrophic gastritisAtrophic gastritis
Impaired acid clearanceImpaired acid clearance GERDGERD
Slowing of gastric emptyingSlowing of gastric emptying Prolong gastric distention Prolong gastric distention ↑ ↑ meal-induced satietymeal-induced satiety
↓ ↓ Ca absorptionCa absorption Bone lossBone loss
Delay in colonic transit Delay in colonic transit ↓ ↓ rectal wall sensitivityrectal wall sensitivity
ConstipationConstipation
↓ ↓ tensile strength in smooth tensile strength in smooth muscle of colonic wallmuscle of colonic wall
DiverticulosisDiverticulosis
↓ ↓ Insulin secretionInsulin secretion ↑ ↑ Insulin resistanceInsulin resistance
EndocrineEndocrine
Thyroid gland – moderate atrophyThyroid gland – moderate atrophy Ovarian failureOvarian failure ↓ ↓ T3 T3 ↓ ↓ DHEADHEA ↑ ↑ PTHPTH ↓ ↓ GH, testosterone, estrogenGH, testosterone, estrogen ↓ ↓ Insulin secretion → Impaired glucose Insulin secretion → Impaired glucose
tolerancetolerance
HematologyHematology
% of marrow space occupied by hematopoietic % of marrow space occupied by hematopoietic tissue declinestissue declines
↓ ↓ stem cells in marrowstem cells in marrow Slowed erythropoiesis ↓ incorporation of iron Slowed erythropoiesis ↓ incorporation of iron
into RBCinto RBC Average values of Hb and hematocrit ↓ Average values of Hb and hematocrit ↓
slightlyslightly
Central Nervous System – StructureCentral Nervous System – Structure
↓ ↓ Brain WeightBrain Weight ↓ ↓ no. of nerve cells in brainno. of nerve cells in brain ↓ ↓ cerebral blood flow (20%)cerebral blood flow (20%) ↑ ↑ neurofibrillary tangles and scattered senile neurofibrillary tangles and scattered senile
plaquesplaques Altered neurotransmittersAltered neurotransmitters
Central Nervous System - FunctionCentral Nervous System - FunctionIntellectIntellect Maintained until at least age 80Maintained until at least age 80 Slowing in central processing Slowing in central processing → Tasks take longer → Tasks take longer
to performto perform
Verbal skillsVerbal skills Maintained until age 70Maintained until age 70 Gradually ↓ in vocabulary, ↑ semantic errors and Gradually ↓ in vocabulary, ↑ semantic errors and
abnormal prosodyabnormal prosody
MentationMentation Difficulty learning, especially languages and Difficulty learning, especially languages and
forgetfulness in non-critical areas – doesn’t impair forgetfulness in non-critical areas – doesn’t impair recall of important memories or affect functionrecall of important memories or affect function
Peripheral Nervous SystemPeripheral Nervous System
↓ ↓ spinal motor neuronsspinal motor neurons
Nerve conduction slowsNerve conduction slows
↓ ↓ vibratory sensation – especially feetvibratory sensation – especially feet
↓ ↓ thermal sensitivity (warm-cool)thermal sensitivity (warm-cool)
↓ ↓ size of large myelinated fiberssize of large myelinated fibers
Musculoskeletal - MuscleMusculoskeletal - Muscle
↓ ↓ muscle fibers → ↓ muscle mass (sarcopenia) muscle fibers → ↓ muscle mass (sarcopenia)
→ lean body mass→ lean body mass
Infiltration of fat into muscle bundlesInfiltration of fat into muscle bundles
↑ ↑ FatigabilityFatigability
↓ ↓ Basal metabolic rate (4%/decade after age Basal metabolic rate (4%/decade after age
50)50)
Musculoskeletal - BoneMusculoskeletal - Bone
↓ ↓ Bone density – both trabecular and cortical boneBone density – both trabecular and cortical bone ↓ ↓ Osteoclast bone formationOsteoclast bone formation ↓ ↓ Bone remodellingBone remodelling ↑ ↑ adipocyte formation in bone marrowadipocyte formation in bone marrow Slower healing of fracturesSlower healing of fractures ↓ ↓ Vitamin D absorption → ↓ osteoblasts → ↓ bone Vitamin D absorption → ↓ osteoblasts → ↓ bone
formationformation ↑ ↑ Bone loss → Loss of height (stooping) and Dorsal Bone loss → Loss of height (stooping) and Dorsal
KyphosisKyphosis ↓ ↓ Bone density & microarchitectural bone deterioration Bone density & microarchitectural bone deterioration
→ Osteoporosis→ Osteoporosis
Musculoskeletal - JointsMusculoskeletal - Joints
Non-articular cartilage grows throughout life Non-articular cartilage grows throughout life
Articular cartilage does changeArticular cartilage does change ↓ ↓ thickness of cartilagethickness of cartilage ↓ ↓ chondrocytes chondrocytes Collagen becomes stiffer → Disordered Collagen becomes stiffer → Disordered
cartilage matrixcartilage matrix As a result, less able to handle mechanical As a result, less able to handle mechanical
stressstress
SkinSkin
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Skin - StructureSkin - Structure
Epidermal changesEpidermal changesMelanocytesMelanocytes
↓ ↓ 15%/decade15%/decade Density doubles on sun-exposed skinDensity doubles on sun-exposed skin ↑ ↑ lentigineslentigines
Langerhans cellsLangerhans cells ↓ ↓ densitydensity ↓ ↓ responsivenessresponsiveness
Dermal ChangesDermal Changes ↓ ↓ collagen – 1% annual decline, altered fiberscollagen – 1% annual decline, altered fibers ↓ ↓ densitydensity Progressive loss of elastic tissue in the papillary dermisProgressive loss of elastic tissue in the papillary dermis
Skin - FunctionSkin - FunctionPhysiologic DecrementPhysiologic Decrement Clinical Consequence (s)Clinical Consequence (s)
↓ ↓ Barrier functionBarrier function DrynessDryness
Slower Cell replacementSlower Cell replacement Rough surface Rough surface Delayed healingDelayed healing
Ineffective DNA repairIneffective DNA repair ↑ ↑ photocarcinogenesisphotocarcinogenesis
↓↓ ElasticityElasticity Lax skinLax skin
↓↓ Immunologic and Immunologic and inflammatory responsivenessinflammatory responsiveness
Chronic low-grade skin Chronic low-grade skin infectionsinfectionsInapparent injuries and infectionsInapparent injuries and infections
Skin – Function (Cont’d)Skin – Function (Cont’d)
Physiologic DecrementPhysiologic Decrement Clinical Consequence (s)Clinical Consequence (s)
Mechanical protection alteredMechanical protection altered↓↓ Sensory perceptionSensory perception
Frequent injuriesFrequent injuries
↓↓ SweatingSweating Tendency to hypothermiaTendency to hypothermia
↓↓ effectiveness of effectiveness of thermoregulation (vascular)thermoregulation (vascular)
Vulnerability to heat and coldVulnerability to heat and cold
↓ ↓ Vitamin D productionVitamin D production OsteomalaciaOsteomalacia
Impaired Wound healingImpaired Wound healing Persistent wounds, weak scarsPersistent wounds, weak scars
Immune systemImmune system ↓ ↓ Cell-Mediated immunityCell-Mediated immunity Lower affinity antibody productionLower affinity antibody production ↓ ↓ delayed-type hypersensitivitydelayed-type hypersensitivity ↑ ↑ Interferon-gamma, TGF-beta, TNF, IL-6, IL-1 production Interferon-gamma, TGF-beta, TNF, IL-6, IL-1 production
causing impaired macrophage functioncausing impaired macrophage function ↑ ↑ circulating IL-6circulating IL-6 ↓ ↓ IL-2 release and IL-2 responsivenessIL-2 release and IL-2 responsiveness ↓ ↓ production of B cells by bone marrowproduction of B cells by bone marrow
Resulting in ↓ immunity contributing to ↓ susceptibility to Resulting in ↓ immunity contributing to ↓ susceptibility to infections and malignancyinfections and malignancy
Sensory - VisionSensory - Vision
Yellowing of lensYellowing of lens
Impaired dark adaptationImpaired dark adaptation
Inability to focus on near items (Presbyopia)Inability to focus on near items (Presbyopia)
↓ ↓ Contrast sensitivity Contrast sensitivity
↓ ↓ Lacrimation → Dry eyesLacrimation → Dry eyes
Sensory – Smell and ThirstSensory – Smell and Thirst
SmellSmell
Detection Detection ↓ by 50%↓ by 50%
ThirstThirst
↓ ↓ thirst drivethirst drive
Impaired control of thirst by endorphinsImpaired control of thirst by endorphins
Sensory - AuditionSensory - Audition Bilateral loss of high frequency tonesBilateral loss of high frequency tones Thickened eardrumThickened eardrum Central processing deficitCentral processing deficit Difficulty discriminating source of soundDifficulty discriminating source of sound Impaired discrimination of target from Impaired discrimination of target from
noisenoise
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